There has been a recent trend in the pharmaceutical market toward the use of pre-filled injectable syringes. These syringes provide benefits of requiring less overfill than traditional syringes, reduced needle-stick injuries, and less risk of cross-infection. Because of these benefits, many of the expensive biological (protein-based) drugs are delivered via pre-filled injectables. However, syringes, unlike ampoules and vials, require a layer of lubricant inside the syringe barrel to facilitate the easy movement of the plunger. As shown in FIG. 1, extractables from the lubricant as well as the packaging containers can cause poisoning and reduced efficacy of these drugs (see, e.g., U.S. Pat. Nos. 5,782,815 and 6,027,481).
FIG. 1 is a schematic illustration of a syringe and the presence of extractables from a lubricant coating from the syringe barrel in injectables of the syringe. FIG. 1 illustrates a syringe containing a drug/biotherapeutic 2 and having a lubricating silicone oil layer 4. The silicone oil droplet 6 leaches into the dispersion, and precipitates as a drug precipitate 8-oligomers on silicone oil droplets.
The lubricants are required to ensure smooth and steady injection of the drug, and to minimize the push force required to administer the drug, once the needle is embedded into the patient's skin. Lack of lubrication can result in non-steady, or excessive force to extract the drug from the container resulting in sudden movement of the needle embedded in the patient's skin leading to pain or injury.
In addition, oxygen and moisture permeation through rubber stoppers can cause denaturing of the drug. That is, protein denaturation due to oxidation is well established in the literature (Anderson et al, Biotech. App. Biochem, v 32, pp 145 (2000)). Ceramic fillers and other additives can be compounded with the polymer stoppers to reduce the oxygen and moisture permeation rates, thus minimizing denaturing due to exposure of the drug to these contaminants over time (see, e.g., U.S. Pat. No. 5,153,039).
The most widely used conventional lubricant for syringe stoppers is silicone oil. Challenges with silicone oil include (1) a high break-force due to migration of silicone oil from between the plunger and the tube during storage, and (2) interaction of the silicone oil with the biological drugs that results in agglomeration and denaturing, thus reducing drug efficacy. Some have addressed these issues by replacing the silicone oil with hard-baked silicone coatings, fluorocarbon films, and non-silicone coatings (e.g. TriboGlide®, which is based on perfluoropolyether chemistries). Although these coatings claim to address the break-force and denaturing issues, the addition of coatings into a manufacturing process adds cost and complexity.
Thus, a need exists for an effective lubrication alternative for stoppers in pharmaceutical applications.